单位：[1]Department of Geriatric Psychiatry, Shanghai Mental Health Center,Shanghai Jiaotong University School of Medicine, Shanghai, China[2]Alzheimer’s Disease and Related Disorders Center, Shanghai JiaotongUniversity, 600 South Wan Ping Road, Shanghai 200030, China[3]XuanwuHospital Capital Medical University, Beijing, China[4]Huashan Hospital, FudanUniversity, Shanghai, China[5]Qilu Hospital of Shandong University, Ji’nan,China[6]West China Hospital of Sichuan University, Chengdu, China四川大学华西医院[7]The FirstAffiliated Hospital of Wenzhou Medical University, Wenzhou, China[8]Guangzhou First People’s Hospital, School of Medicine, South ChinaUniversity of Technology, Guangzhou, China[9]Tianjin Huanhu Hospital,Huanhu Hospital Affiliated to Nankai University, Tianjin, China[10]Departmentof Geriatric Neurology of PLA General Hospital, Beijing, China[11]Departmentof Neurology, Tianjin Medical University General Hospital, Tianjin, China[12]Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China中山大学附属第二医院[13]Fujian Medical University Union Hospital, Fuzhou, China[14]Department ofNeurology, Shanghai General Hospital, Shanghai Jiao Tong University Schoolof Medicine, Shanghai, China[15]Department of Neurology, The First AffiliatedHospital of Xi’an Jiaotong University, Xi’an, China[16]Department ofNeurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine,Shanghai, China[17]Beijing Hospital, Beijing, China[18]Department ofPsychiatry, Sir Run Run Shaw Hospital, Zhejiang University School ofMedicine and Key Laboratory of Medical Neurobiology of Zhejiang Province,Hangzhou, China[19]Northern Jiangsu People’s Hospital, Yangzhou, China江苏省人民医院[20]Department of Neurology, China-Japan Friendship Hospital, Beijing, China[21]Shanghai Changzheng Hospital, Shanghai, China[22]Renji Hospital, ShanghaiJiaotong University School of Medicine, Shanghai, China[23]Department ofNeurology, Zhongnan Hospital of Wuhan University, Wuhan, China[24]Shandong Provinical Hospital affiliated to Shandong University, Ji’nan,China[25]Jiangsu Province People’s Hospital, Nanjing, China[26]PekingUniversity Third Hospital, Beijing, China[27]The First Affiliated Hospital ofChongqing Medical University, Chongqing, China重庆医科大学附属第一医院[28]Department of Geriatricpsychiatry, Wuxi Mental Health Center, Wuxi, China[29]Department ofNeurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China首都医科大学附属天坛医院[30]The First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou, China浙江大学医学院附属第一医院[31]Tongji Hospital of Tongji University, Shanghai, China[32]Xiangya Hospital Central South University, Changsha, China[33]The SecondAffiliated Hospital of Soochow University, Suzhou, China[34]Beijing An DingHospital, Capital Medical University, Beijing, China[35]Peking Union MedicalCollege Hospital, No.1 Shuaifuyuan, Beijing 100730, China[36]Med-X ResearchInstitution, Shanghai Jiao Tong University, Shanghai, China[37]Shanghai GreenValley Pharmaceutical Co.Ltd.,No.421,Niudun Road, Shanghai, China[38]Banner Alzheimer’s Institute, Phoenix, AZ, USA[39]Chamberrs-Grundy Centerfor Transformative Neuroscience, Department of Brain Health, School ofIntegrated Health Sciences, University of Nevada, Las Vegas, USA[40]State KeyLaboratory of Drug Research, Shanghai Institute of Materia Medica, ChineseAcademy of Sciences, 555 Zu chong zhi Road, Nevada, China
Background: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results: A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated.
基金：
Shanghai Green Valley Pharmaceuticals (SHGV); National Science and Technology Major Project for Investigational New Drugs [2011ZX09101-003-01, 2015ZX09101003, 2018ZX09711002-015]
第一作者单位：[1]Department of Geriatric Psychiatry, Shanghai Mental Health Center,Shanghai Jiaotong University School of Medicine, Shanghai, China[2]Alzheimer’s Disease and Related Disorders Center, Shanghai JiaotongUniversity, 600 South Wan Ping Road, Shanghai 200030, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Geriatric Psychiatry, Shanghai Mental Health Center,Shanghai Jiaotong University School of Medicine, Shanghai, China[2]Alzheimer’s Disease and Related Disorders Center, Shanghai JiaotongUniversity, 600 South Wan Ping Road, Shanghai 200030, China
推荐引用方式(GB/T 7714)：
Shifu Xiao,Piu Chan,Tao Wang,et al.A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia[J].ALZHEIMERS RESEARCH & THERAPY.2021,13(1):doi:10.1186/s13195-021-00795-7.
APA：
Shifu Xiao,Piu Chan,Tao Wang,Zhen Hong,Shuzhen Wang...&Zhenxin Zhang.(2021).A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia.ALZHEIMERS RESEARCH & THERAPY,13,(1)
MLA：
Shifu Xiao,et al."A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia".ALZHEIMERS RESEARCH & THERAPY 13..1(2021)
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